S-谷氨基化解开eNOS并调节其细胞和血管功能
Chun-An Chen1, Tse-Yao Wang, Saradhadevi Varadharaj
1Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, Ohio 43210, USA.
Nature
|December 24, 2010
概括
内皮氧化合成酶 (eNOS) 的S-谷氨基化可逆地损害其功能,减少氧化 (NO) 和增加超氧化 (O2) 产生. 在高血压血管中这种修饰与血管扩张功能障碍有关,突出了关键的氧化还原调节机制.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 身体生理学 身体生理学
背景情况:
- 内皮氧化合成酶 (eNOS) 通过产生氧化 (NO) 和超氧化 (O) 来调节血管功能.
- 甲基生物素 (BH(4)) 对于NO合成是必不可少的;它的缺失导致O(2)(•-) 生成.
- 虽然NOS功能障碍与氧化还原应激有关,但BH(4) 补充只能部分恢复功能,这表明其他调节机制.
研究的目的:
- 调查S-谷氨基化,一种可逆的蛋白质修饰,在eNOS功能的氧化还原调节中的作用.
- 为了识别eNOS中涉及氧化还原依赖调节的特定的氨酸残留物.
- 在生理和病理条件下确定eNOS S-glutathionylation对内皮功能和血管扩张的影响.
主要方法:
- 在体外和内皮细胞中研究了氧化应激对eNOS活性和O(2)(•-) 生成的影响.
- 在eNOS上使用生化和蛋白质组方法识别和特征S-glutathionylation位点.
- 评估了eNOS S-glutathionylation对隔离血管内皮依赖血管扩张的功能后果,包括高血压模型中的血管扩张.
主要成果:
- eNOS的S-Glutathionylation可逆地降低其活性,将产量从NO转移到O,主要通过减少酶域.
- 两种保存的氨酸残留物被确定为S-氨基化和ENOS的氧化还原调节的关键部位.
- 在内皮细胞中,eNOS S-Glutathionylation 与血管扩张受损相关,这种功能障碍在高血压血管中被醇特异性降解剂逆转.
结论:
- eNOS的S-氨基化作为一个关键的氧化还原敏感开关,调节其活性和O(2)(•-) 生成.
- 这种修饰在调节细胞信号,内皮功能和血管度方面发挥着重要作用,特别是在氧化应激下.
- 通过减少剂向eNOS S-氨基化,可能为与氧化还原失衡相关的血管功能障碍提供治疗策略.
相关概念视频
02:34Enzymes
68.9K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
68.9K
01:25Protein Glycosylation
8.4K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
8.4K
01:24Oligosaccharide Assembly
2.6K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.6K
01:26Protein Modifications in the RER
5.6K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.6K
01:29Protein Folding Quality Check in the RER
4.4K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.4K
01:02Glucose Homeostasis: Regulation of Blood Glucose
4.3K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
4.3K